Many of the manifestations of periodontal disease resemble the effects of exogenously administered prostaglandins (PGs). When injected subcutaneously, PGs produce blood vessel dilatation and increase in capillary permeability. In tissue culture, PGs stimulate bone resorption. At very low concentrations PGs profoundly stimulate adenylate cyclase in a number of tissues resulting in conversion of ATP to cyclic AMP (c-AMP). Because of the crucial role played by c-AMP in the control of metabolism, and the striking effects PGs can have on the second messenger system, it seems reasonable to suspect that PGs may exert their actions in inflammatory disease states through effects on levels of c-AMP. The overall objectives of our project is: (1) To determine the levels of c-AMP and PGs in human gingival tissue free from inflammatory cells and with various degrees of inflammation as evaluated histologically. (2) To study the effect of exogenous hormonal steroids on the in vitro synthesis of PGE2 and c-AMP. (3) To study the effect of tissue hormones (histamine, bradykinin) and inflammatory agents (carrageenin) on gingival tissue PGE2 and c-AMP. (4) To study the effects of PG inhibitors such as indomethacin and aspirin, and PG antagonists (SC-19220) on the synthesis of gingival PGs.